Antiretroviral therapy in HIV-positive children in Southern Africa
Polly Clayden, HIV i-Base
An article in the August edition of the Lancet Infectious Diseases reported findings from a literature review, conducted by Catherine Sutcliffe and co-workers, looking at 30 paediatric HIV studies or treatment programmes in sub-Saharan Africa. In this assessment, the authors found that children receiving antiretroviral therapy (ART) ranged from infants aged two months to adolescents aged 15 years. Out of 26 studies that reported age at ART initiation, 19 (73%) showed a mean or median age at starting treatment of >5 years. Only two studies reported a median age of starting treatment of <2 years.
The majority of children had severe immunosuppression at initiation of ART. The proportion of children with a CD4 percentage <15% ranged from 56% to 96%.
Only two studies reported how children were referred for treatment. In a Kenyan programme 69% of children were referred following admission to hospital and the remaining children were from other outpatient clinics. In Cote D’Ivoire, the paediatric department or other healthcare settings referred 64% of children, 24% were referred through the people living with HIV/AIDS network and 12% through prevention of mother to child transmission (PMTCT) programmes.
24/30 studies reported the antiretroviral regimens used, the majority (92%) of which included two NRTI inhibitors plus one NNRTI. Typically a regimen of: AZT or d4T plus 3TC with either EFV or NVP.
In the 17 studies that provided information on clinical outcomes, children gained 1.8-3.6 kg in the first year of treatment. There were improvements in weight for age Z scores with a median or mean -2 below baseline with a 1 SD improvement by 3 months. These improvements were sustained 2-3 years after start of treatment in those studies with longer follow up.
There was also significant immunological improvement reported in 28 studies, with a median gain in CD4 percentage of 7.0-13.8% at 6-8 months and 10-16% at 12-15 months of starting ART. And virological data from the 17 studies with the capacity to measure viral load showed a median 2.0 log10 reduction within 1 year. Undetectable viral load was defined differently across studies but for those reporting <250 copies/mL, 400 copies/mL or unknown, 54-55% of children were suppressed at 3 months, 46-81% at 6 months and 49-81% at 12 months after starting treatment.
In the studies reporting <50 copies/mL, undetectable viral load was achieved in 64% and 84% of children at 6 months and 67-100% at 12 months. The authors noted that the explanation for the higher level of suppression in studies using the more sensitive assays was unclear but this trend continued among the small number of children with longer follow up.
Overall mortality during follow up was mostly low with a probability of survival at one year after initiation of ART of 84-97%. A study from Cote D’Ivoire reported over 3 years of follow up, with 92-3% survival at six months, 91% at 12 months, 88% at 18-36 months and 86% at 42 months from initiation of ART.
The majority of deaths were within 6 months of starting treatment. The most commonly reported risk factor for death was low CD4 percentage at initiation of treatment. Age >12-18 months was among the other risk factors. One study from Mozambique compared mortality among children receiving ART and those ineligible for treatment. This comparison found that mortality was higher (HR 3.8, 95% CI 1.9-7.5) for the untreated group despite having better immunological and virological conditions at baseline.
Loss to follow up was generally low: 0-11% and 0.1-7.3% transfers among studies of <1year; 1-9% and 6.0-11.2% transfers, studies of 1-2years and 5.0-7.6% and 15% transfers among studies of up to 3 years.
The authors wrote: “Older children with slower disease progression are more likely to gain access to antiretroviral therapy in sub-Saharan Africa. By contrast, nearly two thirds of HIV-infected children who would have benefited from life prolonging treatment before reaching age 5 years are not being diagnosed or treated.”
This assessment gives a very useful picture of children receiving antiretroviral therapy in sub-Saharan Africa.
As the new WHO recommendations of universal treatment for all infants <12 months begin to be implemented, hopefully the picture should change considerably.
Sutcliffe CG, van Dijk JH, Bolton C et al. Effectiveness of antiretroviral therapy among HIV-infected children in sub-Saharan Africa. Lancet Infect Dis August 2008; 8: 477-89].